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2006 Fiscal Year Final Research Report Summary

The mechanism of the human β-globin gene switching from an aspect of genomic organization.

Research Project

Project/Area Number 16590181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionNippon Medical School

Principal Investigator

KIYAMA Yuko  Nippon Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60234390)

Project Period (FY) 2004 – 2006
Keywordshuman globin gene / transcriptional regulation / switching / bent DNA / genome / chromatin
Research Abstract

The purpose of the study is to investigate the switching mechanism of the human β-globin gene expression from an aspect of its genomic organization. Five active genes (ε-, Gγ-,Aγ-, δ-and (3-globin genes) exhibit temporal and tissue-specific expression during development. In an attempt to examine the regulation of expression of the β-globin gene family from the basis of DNA structure, we focused on a type of non-B DNA structures, intrinsically bent DNA. Using the circular permutation assay, we mapped the bent DNA sites in the entire region of the β-family globin locus and carried out the detail analyses on the region of bent DNA sites. Based on the previous results, the main object of the study supported by a Grant-in-Aid for Scientific Research (C) was to analyze nucleosomal phases in vitro and in vivo in the DNase I hypersensitive sites (HS)-2 enhancer region of the Locus Control Region (LCR).The HS-2 region was flanked by two DNA bend sites and four nucleosomes were accommodated between the sites. The nucleosomal phases that contained the bend core sequences were determined in vitro and in vivo. On the other hand, the nucleosome in the middle which corresponded to the exact location of HS-2 and included the binding site for the erythroid-specific transcription factor NF-E2 showed several phases in erythroid K562 cells. In contrast, only one phase was adopted in non-erythroid HeLa cells in this region. When the chromatin structure is in a repressive state, the transcriptional efficiency is regulated by controlling the interaction of NF-E2 to its cognate motif on the chromosome before chromatin remodeling. From the results, we hypothesized the function of the periodic bent DNA is a basic factor of key nucleosomes on nucleosome alignment. We currently confirmed the hypothesis by screening and characterizing key nucleosomes using a dinucleosome DNA library.

  • Research Products

    (10 results)

All 2006 2005 2004

All Journal Article (9 results) Book (1 results)

  • [Journal Article] in Kiyama R. and Shimizu M. (Eds)2006

    • Author(s)
      Kiyama R. et al.
    • Journal Title

      Transword Research (ISBN: 81-7895-228-9), "DNA Structure, Chromatin and Gene Expression"

      Pages: 252

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biochemical Screening of Stable Dinucleosome Using DNA Fragment from a Dinucleosome DNA Library2005

    • Author(s)
      Kato M.et al.
    • Journal Title

      J. Mol. Biol. 350・2

      Pages: 215-227

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Visualizing forebrain-specific usage of an estrogen receptor alpha promoter2005

    • Author(s)
      Hamada T. et al.
    • Journal Title

      Brain Res. Mol. Brain Res. 139・1

      Pages: 42-51

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Visualizing forebrain-specific usage of an estrogen receptor alpha promoter2005

    • Author(s)
      Hamada T. et al.
    • Journal Title

      Brain Res. Mol. Brain Res. 139 (1)

      Pages: 42-51

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biochemical Screening of Stable Dinucleosome Using DNA Fragment from a Dinucleosome DNA Library2005

    • Author(s)
      Kato M.et al.
    • Journal Title

      J. Mol. Biol. 350 (2)

      Pages: 215-227

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Using a customized DNA microarray for expression profiling of the estrogen responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals2004

    • Author(s)
      Terasaka S. et al.
    • Journal Title

      Environ. Health Perspect. 112・7

      Pages: 773-781

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expressional Regulation of Neuronal and Cancer-Related Genes by Estrogen in Adult Female Rats2004

    • Author(s)
      Rho J.-y.et al.
    • Journal Title

      ENDOCRINE RES. 30・2

      Pages: 257-267

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Using a customized DNA microarray for expression profiling of the estrogen responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals2004

    • Author(s)
      Terasaka S. et al.
    • Journal Title

      Environ. Health Perspect. 112 (7)

      Pages: 773-781

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expressional Regulation of Neuronal and Cancer-Related Genes by Estrogen in Adult Female Rats2004

    • Author(s)
      Rho J.-y.et al.
    • Journal Title

      ENDOCRINE RES 30 (2)

      Pages: 257-267

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] DNA Structure, Chromatin and Gene Expression2006

    • Author(s)
      Kiyama R.et al., Kiyama R., Shiraizu M.編集
    • Total Pages
      252
    • Publisher
      Transworld Research Network
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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